通过CRISPR-Cas9介导在CHMP2B中整合位点特异性杂合突变生成人诱导多能干细胞系。

Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific heterozygous mutation in CHMP2B.

作者信息

Zhang Yu, Schmid Benjamin, Nielsen Troels T, Nielsen Jørgen E, Clausen Christian, Hyttel Poul, Holst Bjørn, Freude Kristine K

机构信息

Stem Cells and Embryology Group, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Bioneer A/S, Hørsholm, Denmark.

出版信息

Stem Cell Res. 2016 Jul;17(1):148-150. doi: 10.1016/j.scr.2016.06.004. Epub 2016 Jun 16.

DOI:10.1016/j.scr.2016.06.004

PMID:27558613

Abstract

Frontotemporal dementia (FTD) is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (FTD3), a component of the endosomal sorting complex required for transport III (ESCRT-III). We have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into one of the alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3.

摘要

额颞叶痴呆（FTD）是一种早发性神经退行性疾病。多个基因的突变会导致家族性FTD，其中之一是位于3号染色体上的带电多囊泡体蛋白2B（CHMP2B）（FTD3），它是转运所需内体分选复合物III（ESCRT-III）的一个组成部分。我们构建了一个健康个体的诱导多能干细胞（iPSC）系，并将CHMP2B IVS5AS G-C基因突变插入其中一个等位基因，导致异常剪接。这个人iPSC系为研究FTD3的CHMP2B依赖性表型提供了一个理想模型。